Procalcitonin (PCT) has become a well-established biomarker for sepsis diagnosis: PCT reflects the severity of bacterial infection and is in particular used to monitor progression of infection into sepsis, severe sepsis, or septic shock. PCT concentrations in sepsis, severe sepsis, or septic shock are typically above 1 ng/mL. It is possible to use PCT to measure the activity of the infection-associated systemic inflammatory response, to control success of therapy, and to estimate prognosis (Assicot M et al.: High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993, 341:515-8; Clec'h C et al.: Diagnostic and prognostic value of procalcitonin in patients with septic shock. Crit Care Med 2004; 32:1166-9; Lee Y J et al.: Predictive comparisons of procalcitonin (PCT) level, arterial ketone body ratio (ABR), APACHE III score and multiple organ dysfunction score (MODS) in systemic inflammatory response syndrome (SIRS), Yonsei Med J 2004, 45, 29-37; Meisner M.: Biomarkers of sepsis: clinically useful? Curr Opin Crit Care 2005, 11, 473-480; Wunder C et al.: Are IL-6, IL-10 and PCT plasma concentrations reliable for outcome prediction in severe sepsis? A comparison with APACHE III and SAPS II. Inflamm Res 2004, 53, 158-163). The increase of PCT levels in patients with sepsis correlates with mortality (Oberhoffer M et al.: Outcome prediction by traditional and new biomarkers of inflammation in patients with sepsis. Clin Chem Lab Med 1999; 37:363-368).
An increasing number of studies discusses the potential role of PCT in non-septic infectious diseases like pneumonia, bacterial meningitis and malaria (Bugden S A et al.: The potential role of procalcitonin in the emergency department management of febrile young adults during a sustained meningococcal epidemic. Emerg Med Australas 2004, 16, 114-119; Chiwakata C B et al.: Procalcitonin as a parameter of disease severity and risk of mortality in patients with Plasmodium falciparum malaria. J Infect Dis 2001, 183, 1161-1164; Schwarz S et al.: Serum procalcitonin levels in bacterial and abacterial meningitis, Crit Care Med 2000, 28, 1828-1832).
In vitro-studies showed that PCT plays an important role during monocyte adhesion and migration and further has an effect on inducible nitric oxide synthase (iNOS) gene expression (Linscheid P et al.: Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes, Crit Care Med 2004, 32, 1715-1721; Wiedermann F J et al.: Migration of human monocytes in response to procalcitonin, Crit Care Med, 2002, 30, 1112-1117; Hoffmarm G et al.: Procalcitonin amplifies inducible nitric oxide synthase gene expression and nitric oxide production in vascular smooth muscle cells, Crit Care Med, 2002, 30, 2091-2095.).
PCT has been used to guide antibiotic therapy (Christ-Crain M et al.: Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial, Lancet. 2004 Feb. 21; 363(9409):600-7.): In patients with symptoms of lower respiratory tract infections presenting at the emergency department PCT was measured, and only patients with PCT concentrations >0.25 ng/mL or >0.5 ng/mL were treated with antibiotics. Apparently, this regimen led to a clinical outcome undistinguishable from the control group, in which also many patients with PCT concentrations <0.25 ng/mL received antibiotics. Of note, in this study, patients with relevant comorbidities as for instance heart failure were excluded. Thus, it is unclear so far, whether the presence of a primary disease in addition to an infection should influence the interpretation of PCT concentrations below 0.25 ng/mL. A relevant primary disease might put an additional burden on the immune system, and biomarkers of infection, such as PCT, in such situation might be indicative of an infection in a different, i.e. lower, concentration range than in the absence of a relevant primary disease.
In healthy individuals, the PCT concentration is well below 0.25 ng/mL: The median concentration has been determined to be 0.014 ng/mL (Morgenthaler N G et al.: Sensitive immunoluminometric assay for the detection of procalcitonin. Clin Chem. 2002 May, 48(5):788-90.)
A method for diagnosis of infections or inflammatory diseases of the airways and lungs with associated heart failure, wherein the biomarker procalcitonin is determined in a patient, is described in WO 2008/040328 A2.